Study to evaluate 3 type of treatment (masitinib + FOLFIRI, or masitinib alone, or FOLFIRI alone) in the treatment of patients with metastatic colorectal cancer that have received 2 or 3 previous therapies

Phase 1

• Conditions: Metastatic colorectal cancer after 2 or 3 previous lines of treatment; MedDRA version: 17.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-000493-30-ES
• Lead Sponsor: AB Science

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-12-16
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

1.Patient with non-resectable metastatic colorectal cancer with histological or cytological documentation of adenocarcinoma of the colon or rectum
2.Patient in third line or fourth line treatment for metastatic colorectal cancer
?in failure of all available therapies : 5FU, irinotecan, oxalplatin +/- bevacizumab,
?for which treatment by cetuximab or panatumumab is not recommended
?for which treatment by regorafenib is not recommended
3.Patient with measurable lesions according to RECIST criteria (version 1.1) with spiral CT scan and defined as ?10 mm in longest diameter and 2X the slice thickness for extra nodal lesions and/or >15 mm in short axis diameter for nodal lesions
4.Patient with ECOG ? 2
5.Patient with adequate organ function
?Absolute neutrophils count (ANC) ? 1.5 x 109/L
?Haemoglobin ? 10 g/dL
?Platelets (PLT) ? 75 x 109/L
?AST/ALT ? 3 x ULN (? 5 x ULN in case of liver metastases)
?Gamma GT ? 2.5 x ULN (? 5 x ULN in case of liver metastases)
?Bilirubin ? 1.5x ULN (? 3xULN in case of liver metastases)
?Normal Creatinine or if abnormal creatinine, creatinine clearance ? 50 mL/min (Cockcroft and Gault formula)
?Albumin > 1 x LLN
?Urea < 2 x ULN
?Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is ? 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
6.Patient with life expectancy > 3 months
7.Patient weight > 40 kg and BMI > 18 kg/m²
8.Female or male patient ? 18 years
9.Man and woman of childbearing potential, who agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake
10.Female patient of childbearing potential must have a negative pregnancy test at screening and baseline
11.Patient able and willing to comply with study visits and procedures as per protocol
12.Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed. If the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable, the designated legal guardian must sign the informed consent
13.Patient able to understand the patient card and to follow the patient card procedures, in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity during the first 2 months of treatment
14.Patient affiliated to a social security regimen
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1.Prior treatment with masitinib, or any other tyrosine kinase inhibitor for the treatment of malignancy, except regorafenib,
2.More than 3 prior chemotherapy regimens for metastatic colorectal cancer.
3.Pregnant, intent to be pregnant, or nursing female patient
4.Patient with any chronic inflammatory bowel disease
5.Patient treated for a cancer other than colorectal cancer within five years before enrollment, with the exception of basal cell carcinoma or cervical cancer in situ
6.Patient with an hepatic involvement > 50%
7.Patient with active central nervous system (CNS) metastasis or history of CNS metastases.
8.Patient with an active infection (Human immunodeficiency virus infection and/or hepatitis B or C infection ?)
9.Patient presenting with cardiac disorders defined by at least one of the following conditions:
?Patient with recent cardiac history (within 6 months) of:
-Acute coronary syndrome
-Acute heart failure (class III or IV of the NYHA classification)
-Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
?Patient with cardiac failure class III or IV of the NYHA classification
?Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
?Syncope without known aetiology within 3 months
?Uncontrolled severe hypertension, according to the judgement of the investigator, or symptomatic hypertension
10.Patient with a history of poor compliance or of drug/alcohol abuse, or excessive alcohol beverage consumption, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
WASH-OUT
11.Any previous treatment with an investigational agent or chemotherapy or biological agent will require a wash-out period of four weeks prior to baseline

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Overall survival (OS);Secondary Objective: ?Survival rate every 6 months<br>?Tumor assessment<br>-Overall Progression Free Survival (PFS)<br>-PFS rate every 8 weeks<br>-Overall Time To Progression (TTP)<br>-TTP rate every 8 weeks <br>-Best response rate <br>-Objective response rate (CR + PR) and Disease control rate (CR + PR + SD) every 8 weeks<br>?Tumor marker: Carcino-Embryonic Antigen (CEA, ng/ml) every 8 weeks<br>?Quality of life assessment every 8 weeks <br>-ECOG Performance Status<br>-Quality of Life according to the EORTC QLQ-C30<br>-Analgesic intake<br>-Pain improvement (visual analog scale: VAS)<br>?Pharmacogenomic assessment (Relationship between genomic data and overall survival)<br>?Safety profile using the NCI CTCAE v4.02 classification;Primary end point(s): Overall Survival (OS) is defined as the time from the randomization to the date of documented death;Timepoint(s) of evaluation of this end point: Date of documented death.